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Exploring the Evolution of Novel Enzyme Functions within Structurally Defined Protein Superfamilies

Nicholas Furnham, Ian Sillitoe, Gemma L. Holliday, Alison L. Cuff, Roman A. Laskowski, Christine A. Orengo, Janet M. Thornton, Yanay Ofran
2012 PLoS Computational Biology  
The evolution of enzyme function in the isomerases.  ...  With completely sequenced genomes, the full complement of enzymes in an organism can be defined, and 3D structures have been determined for many enzyme families.  ...  We have adopted a number of approaches to define the functional impact of these mutations on myosin function.  ... 
doi:10.1371/journal.pcbi.1002403 pmid:22396634 pmcid:PMC3291543 fatcat:77jw2t4jjbgarjsgexccje34iy

FunTree: advances in a resource for exploring and contextualising protein function evolution

Ian Sillitoe, Nicholas Furnham
2015 Nucleic Acids Research  
This allows the investigation of how novel functions have evolved within a structurally defined superfamily and provides a means to analyse trends across many superfamilies.  ...  This is done not only within the context of a protein's sequence and structure but also the relationships of their functions.  ...  Christine Orengo for useful comments and suggestions as well as the European Bioinformatics Institute for the use of their highperformance computing cluster in processing the data.  ... 
doi:10.1093/nar/gkv1274 pmid:26590404 pmcid:PMC4702901 fatcat:qnfbhibpjfapfd3kanbp6nqcx4

Large-Scale Analysis Exploring Evolution of Catalytic Machineries and Mechanisms in Enzyme Superfamilies

Nicholas Furnham, Natalie L. Dawson, Syed A. Rahman, Janet M. Thornton, Christine A. Orengo
2016 Journal of Molecular Biology  
Using a range of computational tools and resources, we have compiled information on all experimentally annotated changes in enzyme function within 379 structurally defined protein domain superfamilies,  ...  Additionally, we use structural information of the enzymes active site to examine how different superfamilies have changed their catalytic machinery during evolution.  ...  Fig. 4 . 4 Summary of top 10 bond types that are gained and lost through the evolution of enzyme function within 379 domain superfamilies.  ... 
doi:10.1016/j.jmb.2015.11.010 pmid:26585402 pmcid:PMC4751976 fatcat:rqkj2aj7nrbhzngzy7q3sppquq

FunTree: a resource for exploring the functional evolution of structurally defined enzyme superfamilies

N. Furnham, I. Sillitoe, G. L. Holliday, A. L. Cuff, S. A. Rahman, R. A. Laskowski, C. A. Orengo, J. M. Thornton
2011 Nucleic Acids Research  
Gathering together this range of data into a single resource allows the investigation of how novel enzyme functions have evolved within a structurally defined superfamily as well as providing a means to  ...  This is done not only within the context of an enzyme's sequence and structure but also the relationships of their reactions.  ...  Bringing together this range of data into a single resource allows the investigation of the evolution of novel enzyme functions within structurally defined superfamilies.  ... 
doi:10.1093/nar/gkr852 pmid:22006843 pmcid:PMC3245072 fatcat:lwlpp7cazvdy5ebfxequzzujnu

Exploring the structure and function paradigm

Oliver C. Redfern, Benoit Dessailly, Christine A. Orengo
2008 Current Opinion in Structural Biology  
Many of these structures are novel -using the 5Å threshold defined above for fold similarity).  ...  A detailed analysis of limited sets of superfamilies recently culminated in the development of a new resource for the study of structure-function relationships within enzyme superfamilies, namely the Structure  ... 
doi:10.1016/j.sbi.2008.05.007 pmid:18554899 pmcid:PMC2561214 fatcat:ds3bhbjjqjf3ljcroed3uonc4e

New Insights about Enzyme Evolution from Large Scale Studies of Sequence and Structure Relationships

Shoshana D. Brown, Patricia C. Babbitt
2014 Journal of Biological Chemistry  
Comparison among all of the sequences and/or structures in a superfamily can then be used to deduce how evolution has varied these features to produce new enzyme functions from the ancestral structural  ...  We illustrate here some major themes emerging from large scale studies of functionally diverse enzyme superfamilies that impact our understanding of the evolution of enzyme function.  ...  The concept of moonlighting enzymes, describing additional structural or regulatory functions performed in addition to their catalytic functions, has also provided novel insight about the evolution of  ... 
doi:10.1074/jbc.r114.569350 pmid:25210038 pmcid:PMC4215206 fatcat:biiui2rljngshklchfp6465hom

MANET: tracing evolution of protein architecture in metabolic networks

Hee Shin Kim, Jay E Mittenthal, Gustavo Caetano-Anollés
2006 BMC Bioinformatics  
depicting the evolution of protein fold architecture.  ...  Our aim is to find evolutionary patterns and processes embedded in the architecture and function of modern metabolism, using information derived from structural genomics.  ...  Any opinions, findings, and conclusions or recommendations expressed in this material are those of the authors and do not necessarily reflect the views of the funding agencies.  ... 
doi:10.1186/1471-2105-7-351 pmid:16854231 pmcid:PMC1559654 fatcat:vdp6uhww7jau3nkczazhlfcnsy

Evolutionary Origin of a Secondary Structure: π-Helices as Cryptic but Widespread Insertional Variations of α-Helices That Enhance Protein Functionality

Richard B. Cooley, Daniel J. Arp, P. Andrew Karplus
2010 Journal of Molecular Biology  
This new understanding of π-helices paves the way for this generally overlooked motif to become a noteworthy feature that will aid tracing the evolution of many protein families, guide investigations of  ...  a "missing link" intermediary form of the ribonucleotide reductase family, vestigial π-helices, and a novel function for π-helices we term peristaltic-like shifts.  ...  Acknowledgments We thank Joe Thornton, Jacque Fetrow and Brian Matthews for critique of an earlier manuscript.  ... 
doi:10.1016/j.jmb.2010.09.034 pmid:20888342 pmcid:PMC2981643 fatcat:777cruvrgzb5xamctplnlg56e4

New computational approaches to understanding molecular protein function

Jacquelyn S. Fetrow, Patricia C. Babbitt
2018 PLoS Computational Biology  
functions within a protein superfamily-that is, the number of clusters that captures biologically relevant functional boundaries that correlate with the level of molecular functional hierarchy being pursued  ...  The Structure-Function Linkage Database (SFLD) also defines a molecular functional hierarchy, in this case as superfamily, subgroup, and family (Fig 1) [26].  ... 
doi:10.1371/journal.pcbi.1005756 pmid:29621256 pmcid:PMC5886384 fatcat:5f3gv2hx25awlfaod3thv67j5u

Understanding enzyme function evolution from a computational perspective

Jonathan D Tyzack, Nicholas Furnham, Ian Sillitoe, Christine M Orengo, Janet M Thornton
2017 Current Opinion in Structural Biology  
In this review, we will explore recent computational approaches to understand enzyme evolution from the perspective of protein structure, dynamics and promiscuity.  ...  We will present quantitative methods to measure the size of evolutionary steps within a structural domain, allowing the correlation between change in substrate and domain structure to be assessed, and  ...  A review of integrative approaches to explore enzyme evolution and functional diversity within enzyme superfamilies, highlighting recent large-scale experimental methods to determine activity profiles  ... 
doi:10.1016/j.sbi.2017.08.003 pmid:28892668 fatcat:ph7tbjfqevdqhiai4dkuwmygmy

Proteins with Class α/β Fold Have High-level Participation in Fusion Events

Sujun Hua, Tao Guo, Julian Gough, Zhirong Sun
2002 Journal of Molecular Biology  
An exhaustive survey of fusion events within 30 completely sequenced genomes and subsequent structure annotations to the component proteins at a SCOP superfamily level with hidden Markov models was carried  ...  Here, we took a new approach to the analysis of the structural features of the proteins involved in fusion events.  ...  This work was funded by the National Natural Science Grant in China (no. 39980007) and the National Key Foundational Research Grant in China (985, 863).  ... 
doi:10.1016/s0022-2836(02)00467-9 pmid:12095249 fatcat:vjr5sn3agzhdrg6yv2onulsvda

The history of the CATH structural classification of protein domains

Ian Sillitoe, Natalie Dawson, Janet Thornton, Christine Orengo
2015 Biochimie  
The establishment of comprehensive function annotation resources has also meant that domain families can be functionally annotated allowing insights into functional divergence and evolution within protein  ...  We review the expansion of the CATH and SCOP resources to capture predicted domain structures in the genome sequence data and to provide information on the likely functions of proteins mediated by their  ...  too, allowing large scale studies of the divergence of function within superfamilies during evolution.  ... 
doi:10.1016/j.biochi.2015.08.004 pmid:26253692 pmcid:PMC4678953 fatcat:jb7v7o2f3fc37fjoc2lopkcy44

Functional innovation from changes in protein domains and their combinations

Jonathan G Lees, Natalie L Dawson, Ian Sillitoe, Christine A Orengo
2016 Current Opinion in Structural Biology  
Domains are the functional building blocks of proteins. In this work we discuss how domains can contribute to the evolution of new functions.  ...  Domains themselves can evolve through various mechanisms, altering their intrinsic function. Domains can also facilitate functional innovations by combining with other domains to make novel proteins.  ...  Domain insertions can act to drive the evolution of new functions such as in the large structurally and functionally diverse HADSF enzyme superfamily (Huang et al. 2015) , here different levels of promiscuity  ... 
doi:10.1016/j.sbi.2016.05.016 pmid:27309309 fatcat:vykx2i6uabfazpwv4oozsyxnle

Leveraging Enzyme Structure−Function Relationships for Functional Inference and Experimental Design: The Structure−Function Linkage Database†

Scott C.-H. Pegg, Shoshana D. Brown, Sunil Ojha, Jennifer Seffernick, Elaine C. Meng, John H. Morris, Patricia J. Chang, Conrad C. Huang, Thomas E. Ferrin, Patricia C. Babbitt
2006 Biochemistry  
We present the results of analyses using the SFLD in correcting misannotations, guiding protein engineering experiments, and elucidating the function of recently solved enzyme structures from the structural  ...  residuesshelps elucidate the structure-function relationships of enzymes.  ...  Enzyme functional domains are defined in the SFLD as the functional domains of individual enzymatic proteins.  ... 
doi:10.1021/bi052101l pmid:16489747 fatcat:dajbxfc4ajbq3hckmbou2ep2v4

Zebra2: advanced and easy-to-use web-server for bioinformatic analysis of subfamily-specific and conserved positions in diverse protein superfamilies

Dmitry Suplatov, Yana Sharapova, Elizaveta Geraseva, Vytas Švedas
2020 Nucleic Acids Research  
functions within a shared 3D-structure of the superfamily, determine common and specific patterns of function-associated local structural elements, assist to select hot-spots for rational design and to  ...  Zebra2 is a highly automated web-tool to search for subfamily-specific and conserved positions (i.e. the determinants of functional diversity as well as the key catalytic and structural residues) in protein  ...  ACKNOWLEDGEMENTS The use of HPC computing resources at the Lomonosov Moscow State University supported by the project RFMEFI62117X0011 to prepare the PDB and UniProt databases in a format compatible with  ... 
doi:10.1093/nar/gkaa276 pmid:32313959 fatcat:3gmxnpwn6zapvhiwiipk7scfay
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